.alpha.-Chloroalprazolam and .alpha.-chlorotriazolam are known, see U.S. Pat. No. 4,250,094 (Preparation 2) and No. 4,141,902 (Example 7), respectively. U.S. Pat. No. 4,141,902 also generically discloses .alpha.-bromoalprazolam and .alpha.-bromotriazolam.
Adinazolam and the 6-(o-chlorophenyl) analog of adinazolam are known, see U.S. Pat. No. 4,250,094, Examples 1 and 2, respectively.
The transformation of .alpha.-chloroalprazolam to adinazolam is known, see U.S. Pat. No. 4,250,094, Example 1. The aminolysis of .alpha.-bromoalprazolam and .alpha.-bromotriazolam is also generically known.
Various processes are known for the preparation of .alpha.-chloroalprazolam, none of which are direct chlorination of the triazolo methyl group, see, for example, U.S. Pat. Nos. 4,235,775, 4,141,902 (Example 1), 4,250,094, and J. Med. Chem., 23, 392 (1980).
The process of the present invention involves direct halogenation of the triazolo methyl group of alprazolam to produce .alpha.-chloroalprazolam or .alpha.-bromoalprazolam.